Helicobacter pylori factors involved in the development of gastroduodenal mucosal damage and ulceration.
Many putative virulence determinants of Helicobacter pylori are believed to trigger and worsen the gastroduodenal mucosa damage observed in infected patients. H. pylori urease reacts with the gastric urea and generates ammonia; ammonia combines with water and yields ammonium hydroxide, which is cytotoxic. Ammonia may also inhibit cell proliferation and cause indirect mucosal injury by stimulating neutrophils. Phospholipases may damage the gastric mucosa by degrading phospholipids and generating precursors of ulcerogenic components. Other enzymes, such as protease, neuraminidase, fucosidase, and alcohol dehydrogenase, can contribute to damage of the gastric epithelium by destroying the integrity of mucus or by inducing lipid peroxidation. Infection by vacuolating cytotoxic (VacA+) H. pylori strains is considered to constitute increased risk for development of peptic ulcer and gastric cancer. Exploration of the vacA gene structure has shown the existence of strongly toxigenic strains, and has confirmed at the molecular level the increased ulcerogenic potential of VacA+ H. pylori strains. A pathogenicity island called cag has been recently described in Type 1 H. pylori strains (VacA+/CagA+).cag contains the cagA gene (whose expression is associated with toxigenicity) and many genes, some of which are highly homologous to virulence genes of other virulent bacteria, that account for the enhanced pathogenic potential of CagA+ organisms.
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Institute of Internal Medicine, University of Siena, Italy.
D000818:Animals; D000942:Antigens, Bacterial / Q000009:adverse effects; D001426:Bacterial Proteins / Q000009:adverse effects; D001427:Bacterial Toxins / Q000009:adverse effects; D005753:Gastric Mucosa / Q000382:microbiology; D005756:Gastritis / Q000382:microbiology*; D016481:Helicobacter Infections; D016480:Helicobacter pylori / Q000201:enzymology / Q000472:pathogenicity; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology; D010437:Peptic Ulcer / Q000382:microbiology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori